Regional cerebral blood volume (CBV) and its dynamic change induced by neural activity are critical indices for evaluating tissue viability and function. Routine magnetic resonance imaging (MRI) of CBV in humans currently requires injection of gadolinium-based blood contrast agents, hampering repeated measurements and potentially causing nephrogenic systemic fibrosis. Therefore, alternative non-invasive techniques are required for CBV mapping in humans. Importantly, compartment-specific CBV measurements will be crucial to obtain insight into blood flow regulation during physiological responses, because arterial vessels dilate and constrict to actively control cerebral blood flow (CBF), while venous vessels respond passively. In this application, we propose in humans at 3 Tesla to evaluate and implement non-invasive, arterial CBV measurement techniques without contrast agents, to perform quantitative mapping of baseline arterial CBV, and to determine its relative change during stimulation. The hypotheses to be tested are to determine whether quantitative arterial CBV can be reliably mapped in humans by non-invasive MRI techniques and to determine whether the arterial CBV change is significant during neural activity in humans. Baseline arterial CBV can be measured by our recent arterial spin-labeling techniques, which have been successfully applied to quantitatively map arterial CBV and CBF in animals. Translation to 3-T awake human studies necessitates consideration of differences in species, physiological conditions, and magnetic field strengths. Therefore we will carefully evaluate and optimize human techniques for arterial CBV measurement, and examine the consistency of arterial CBV quantification. During stimulation, it is often assumed that the arterial CBV change is minimal and therefore can be ignored in functional MRI (fMRI) studies. However, this notion has recently been challenged by our animal studies showing that the arterial CBV increase is the dominant contribution to the total CBV response. Thus, we propose to apply this arterial CBV-based fMRI technique to humans to determine dynamic changes and spatial specificity of arterial CBV and 'true'BOLD signals during neural stimulation. The goal of these investigations is to implement non-invasive blood volume mapping techniques for routine human imaging without the injection of contrast agents, which will enable future diagnosis and study of vascular disease. PUBLIC HEALTH RELEVANCE: Develop noval non-invasive MR blood volume imaging techniques and to measure baseline cerebral blood volume and its changes during stimulation in humans.